Synaptic transmission is the process by which neurons communicate by excitatory (generation of an action potential) or inhibitory (inhibition of an action potential following excitation) mechanisms. Excitatory synaptic transmission often occurs by means of the neurotransmitter L-glutamate and its cognate glutamate receptors, which include the N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype glutamate receptors. Synaptic plasticity refers to the use-dependent ability of post-synaptic neurons to modulate their response to the release of neurotransmitters during synaptic transmission, and is thought to be important in learning and memory processes.
The excessive stimulation of post-synaptic neurons (a phenomenon known as “excitotoxicity”), which can lead to neuronal death or apoptosis, has been implicated in a variety of central nervous system (CNS) disorders. Activation of the NMDA receptor may induce programmed cell death (apoptosis) in cultured hippocampal neurons, and may underlie the loss of neurons and neuronal function in central nervous system disorders ranging from acute brain trauma and stroke to neurodegenerative diseases such as Huntington's, Alzheimer's, and Parkinson's Diseases.1-5 
NMDA receptor activation may also lead to facilitation of clathrin-mediated endocytosis of AMPA receptors, which mediate fast synaptic transmission at excitatory synapses in the mammalian CNS.6;7 AMPA receptor function can be modified at the level of open channel probability34, channel conductance27;33, and the kinetics of desensitization.52 Rapid redistribution of AMPA receptors to and from the postsynaptic domain is also thought to be a means of regulating the strength of AMPA receptor-mediated synaptic transmission.43;45;6 AMPA receptors undergo functionally distinct constitutive and regulated clathrin-dependent cycling between intracellular compartments and the plasma membrane via vesicle-mediated plasma membrane insertion (exocytosis) and internalization (endocytosis).22;30;20;24;41;14 Regulating these processes can lead to rapid changes in the number of AMPA receptors expressed in the postsynaptic membrane, thereby contributing to the expression of certain forms of synaptic plasticity, including hippocampal long term potentiation (LTP)35;42;50 and long term depression (LTD) in the cerebellum and hippocampus.14;24;25;44 AMPA receptors may be subjected to stimulated endocytosis by diverse stimuli including growth factors, such as insulin/IGF-114;25, agonist binding22;21;20 and LTD-producing protocols.24;14;25 